Impact of Progesterone on Molecular Mechanisms of Preterm Premature Rupture of Membranes

Mechanisms of Immune Tolerance and Inflammation via Gonadal Steroid Hormones in Preterm Birth

“…Progesterone stimulation promotes the expression of toll-like receptor (TLR) 2, TLR-5, and nucleotide-binding oligomerization domain containing 2 (NOD2). However, it did not affect the expression of the TLR4 and NOD1 genes, alone or in combination with TLR/NOD-like receptor (NLR) agonists, but it suppressed the expression of IL-1β and IL-8, which are upregulated by TLR2, TLR5, and NOD2 agonists 35 . Progesterone is reported to suppress the expression of the proapoptotic factors, Bax and Bid, which are induced by stimulation with proinflammatory cytokines (TNF-α, IL-18, and IL-1β) and thrombin 35 .…”

“…However, it did not affect the expression of the TLR4 and NOD1 genes, alone or in combination with TLR/NOD-like receptor (NLR) agonists, but it suppressed the expression of IL-1β and IL-8, which are upregulated by TLR2, TLR5, and NOD2 agonists 35 . Progesterone is reported to suppress the expression of the proapoptotic factors, Bax and Bid, which are induced by stimulation with proinflammatory cytokines (TNF-α, IL-18, and IL-1β) and thrombin 35 . These reports indicate that progesterone is closely involved in inflammatory responses during pregnancy.…”

“…It is increasingly acknowledged that an abnormal maternal immune system can cause PTB via premature activation of inflammatory pathways 43 . Progesterone protects from pPROM via anti-inflammatory and antithrombogenic effects on term human fetal amniotic membrane cells 35 . RU486, a progesterone antagonist, is reported to cause PTB in mice, probably through elevated levels of decidual prostaglandin E2 (PGE2) and IL-6 44 .…”

“…35 Progesterone is reported to suppress the expression of the proapoptotic factors, Bax and Bid, which are induced by stimulation with proinflammatory cytokines (TNF-α, IL-18, and IL-1β) and thrombin. 35 These reports indicate that progesterone is closely involved in inflammatory responses during pregnancy. With regard to maternal inflammation triggers, it has been shown that progesterone suppresses the expression of monocyte chemotaxis protein 1, which contributes to monocyte recruitment into the myometrium.…”

“…43 Progesterone protects from pPROM via anti-inflammatory and antithrombogenic effects on term human fetal amniotic membrane cells. 35 RU486, a progesterone antagonist, is reported to cause PTB in mice, probably through elevated levels of decidual prostaglandin E2 (PGE2) and IL-6. 44 The concentrations of IL-6, IL-21, and TNF-a, as well as PR-A expression by CD19+ B cells, have been identified as maternal plasma markers of sPTB and their levels are higher in PTB patients than in term delivery cases.…”